Hydrochloric Acid → tert-Butyl ((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)carbamate

HRID 1406580Notes

Reaction equation

HRID 1406580 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11](=[O:22])[C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])[CH:9]=[CH:10][C:2]1=2.CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].CC(O)C.Cl>C1(C)C=CC=CC=1>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C@@H:11]([OH:22])[C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[CH3:13])[CH:9]=[CH:10][C:2]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 11143Aluminum isopropoxideHCID 59339713(S)-tert-butyl 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxopropan-2-ylcarbamate

Product 1

HCID 59339843tert-Butyl ((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The diastereoselective catalytic Meerwein-Ponndorf-Verley reduction was made by the method described by Jingjun Yin et. al. J. Org. Chem. 2006, 71, 840-843. (S)-tert-butyl 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxopropan-2-ylcarbamate (I2b) (3.76 g, 12.23 mmol), aluminium isopropoxide (0.5 g, 2.45 mmol) and 2-propanol (12 mL, 157.75 mmol) in toluene (22 mL) was stirred at +50° C. under argon for 16 hours. The reaction mixture was poured into 1M HCl (150 mL), the mixture was extracted with EtOAc (250 mL). The organic phase was washed with water (2×50 mL) and brine (100 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash-chromatography on silica using EtOAc:Hexane (1:2) as eluent. Fractions containing product was combined. Solvent was removed by evaporation to give the desired product as a colourless solid. Yield 3.19 g (84%)

Workup

  1. extractionthe mixture was extracted with EtOAc (250 mL)
  2. washThe organic phase was washed with water (2×50 mL) and brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash-chromatography on silica
  7. additionFractions containing product
  8. customSolvent was removed by evaporation

Sources & evidence

ORD record
ord-da239a3736e446cdbb8dbc304bf0b013
Source dataset
uspto-grants-2014_12
Patent number
US08916600B2

Reaction notes

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